Dr. Caroline Westwater

Education:
BSc (Hons.) Biochemistry, Heriot-Watt University, Scotland, UK
PhD Molecular Mycology, University of Aberdeen, Scotland, UK
Postdoctoral Training: Paterson Institute for Cancer Research, University of Manchester, England, UK
Postdoctoral Training: Department of Microbiology and Immunology, Medical University of South Carolina, SC

Honors and Awards:
Grant reviewer US CRDF First Steps to Market Program (2004-2005)
Temporary Member, NIAID Microbiology & Infectious Diseases Study Section (2005)
Grant reviewer Swiss Federal Institute Research Commission (2005)
Grant reviewer Israel Science Foundation (2005-2006)
Grant reviewer US CRDF Science Center Programs (2006)
Member of Journal of Infectious Diseases Editorial Advisory Board (2006-present)
Chair, Candida session, IADR/AADR Annual Meeting, Orlando, FL (2006)
Chair, Infectious Diseases session, IADR/AADR Annual Meeting, New Orleans, LA (2007)
ASM Candida and Candidiasis: Post-Doctoral/Junior Faculty Travel Award Winner (2008)
DeA Young Investigator Travel Award Winner (2008)

Manuscript reviewer: Journal of Infectious Diseases (editorial board since 2006), Yeast, Medical Mycology, Eukaryotic Cell, Journal of Clinical Microbiology, BMC Microbiology, Applied and Environmental Microbiology, Glycobiology

Department Affiliations:
Craniofacial Biology, College of Dental Medicine
Microbiology & Immunology, College of Medicine
Molecular and Cellular Biology and Pathobiology Program, College of Graduate Studies

Research Interests:
The Westwater lab primarily studies the human fungal pathogen Candida, which is responsible for an array of infections in both immunocompetent and immunocompromised hosts. This opportunistic pathogen can cause a wide variety of clinical disorders ranging from infections of the mucosa to life-threatening systemic disease. Our research focus is centered on the investigation of Candida pathogenicity at its most fundamental level- the point where the host and fungus interacts.

Examples of current research projects

Project 1: Candida glabrata gene activation during infectionCandida species are the most common fungal pathogen of humans, with Candida albicans and Candida glabrata accounting for 70-80% of all clinical cases. Over the last decade C. glabrata has emerged as a significant and formidable pathogen. Besides its high degree of drug resistance, only a few virulence attributes have been identified and infection mechanisms remain poorly understood. Our knowledge is not only incomplete but is also significantly lacking; therefore, the basis for C. glabrata pathogenicity remains unclear. Because C. glabrata and C. albicans are evolutionarily divergent their association with the mammalian host most likely evolved independently. This view is reinforced by the fact that C. glabrata lacks many of the ÔclassicalÕ virulence factors deemed important for C. albicans invasion of host tissues. Despite these deficits C. glabrata and C. albicans produce a similar array of infections in humans (e.g. oral, vaginal, deep-seated and systemic disease). Thus, the long-term goal of this project is to delineate the molecular mechanisms required for C. glabrata colonization, persistence, and infection of mammalian tissues

Project 2: In vivo induction of Candida albicans morphogenesisCandida albicans can switch between three distinct morphological forms: yeast, hyphae, and pseudohyphae. The reversible transition between the unicellular (yeast) and filamentous (pseudohyphal/hyphal) state contributes significantly to the fungal invasion- and pathogenic-process. Thus, there is a great impetus to understand the signals and regulatory pathways that govern the yeast-filament-yeast switch. Strains with defined mutations in terminal signaling components exhibit severe defects in this process; however, the original notion that these mutants are ÔlockedÕ in one growth form has been overturned, mainly because the context (or environment) in which the switch occurs is often not considered. This notion is exemplified by the homozygous double knockout of the terminal transcription factors EFG1 and CPH1. For instance, the efg1Æ/cph1Æ mutant displays severe morphological defects in a tissue culture-based model of mucosal candidiasis, but forms invasive filaments in some, but not all, mammalian tissues in vivo. These results emphasize the existence of other independent in vivo filamentation pathways and tissue-specific effects on morphogenesis. Thus, the long-term goal of this project is to identify the genetic program responsible for stimulating filamentous growth at the in vivo mammalian mucosal surface.

Recent Publications:

Schofield DA and Westwater C. 2009. Phage-mediated bioluminescent detection of Bacillus anthracis. J Appl Microbiol, [EPub ahead of print April 24]. PMID: 19426264.

Westwater C, Schofield DA, Nicholas PJ, Paulling EE and Balish E. 2007. Candida glabrata and Candida albicans; dissimilar tissue tropism and infectivity in a gnotobiotic model of mucosal candidiasis. FEMS Immunol Med Microbiol, 51(1):134-139. PMID: 17854475.

Westwater C, Balish E, Warner TF, Nicholas PJ, Paulling EE and Schofield DA. 2007. Susceptibility of gnotobiotic transgenic mice (Tgepsilon26) with combined deficiencies in natural killer cells and T cells to wild-type and hyphal signaling-defective mutants of Candida albicans. J Med Microbiol, 56(9):1138-44 (selected for front cover article). PMID: 17761474.

Schofield DA, Westwater C, Barth JL and DiNovo AA. 2007. Development of a yeast biosensor-biocatalyst for the detection and biodegradation of the organophosphate paraoxon. Appl Microbiol Biotechnol, 76(6):1383-1394. PMID: 17665192.

Westwater C, Balish E and Schofield DA. 2005. Candida albicans-conditioned medium protects yeast cells from oxidative stress: a possible link between quorum sensing and oxidative stress resistance. Eukaryot Cell, 4(10):1654-1661. PMID: 16215173, PMCID: PMC1265892.

Schofield DA, Westwater C and Balish E. 2005. Divergent chemokine, cytokine and beta-defensin responses to gastric candidiasis in immunocompetent C57BL/6 and BALB/c mice. J Med Microbiol, 54(1):87-92 (selected for front cover article). PMID: 15591261.

Schofield DA, Westwater C, Warner T and Balish E. 2005. Differential Candida albicans lipase gene expression during alimentary tract colonization and infection. FEMS Microbiol Lett, 244 (2):359-365. PMID: 15766791.

Balish E, Warner TF, Nicholas PJ, Paulling EE, Westwater C and Schofield DA. 2005. Susceptibility of germfree phagocyte oxidase- and nitric oxide synthase 2-deficient mice, defective in the production of reactive metabolites of both oxygen and nitrogen, to mucosal and systemic candidiasis of endogenous origin. Infect Immun, 73(3):1313-1320. PMID: 15731028, PMCID: PMC1064974.

Munro CA, Bates S, Buurman ET, Hughes HB, MacCallum DM, Bertram G, Atrih A, Ferguson MA, Bain JM, Brand A, Hamilton S, Westwater C, Thomson LM, Brown AJ, Odds FC and Gow NA. 2005. Mnt1p and Mnt2p of Candida albicans are partially redundant alpha-1,2-mannosyltransferases that participate in O-linked mannosylation and are required for adhesion and virulence. J Biol Chem, 280(2):1051-1060. PMID: 15519997.

Schofield DA, Westwater C and Balish E. 2004. Beta-defensin expression in immunocompetent and immunodeficient germfree and Candida albicans monoassociated mice. J Infect Dis, 190(7):1327-1334. PMID: 15346345.

Westwater C, Kasman LM, Schofield DA, Werner PA, Dolan JW, Schmidt MG and Norris JS. 2003. Use of genetically engineered phage to deliver antimicrobial agents to bacteria: an alternative therapy for the treatment of bacterial infections. Antimicrob Agents Chemother, 47(4):1301-1307 (selected for Journal Highlights, ASM News 69:5, 2003). PMID: 12654662, PMCID: PMC152521.

Schofield DA, Westwater C, Hoel BD, Werner PA, Norris JS and Schmidt MG. 2003. Development of a thermally regulated broad-spectrum promoter system for use in pathogenic Gram-positive species. Appl Environ Microbiol, 69(6):3385-3392. PMID:12788740, PMCID: PMC161472.

Schofield DA, Westwater C, Warner T, Nicholas PJ, Paulling EE and Balish E. 2003. Hydrolytic gene expression during oroesophageal and gastric candidiasis in immunocompetent and immunodeficient gnotobiotic mice. J Infect Dis, 188(4):591-599 (selected for front cover article). PMID: 12898449.

Schofield DA, Westwater C, Paulling EE, Nicholas PJ and Balish E. 2003. Detection of Candida albicans mRNA from formalin-fixed, paraffin-embedded mouse tissues by nested reverse transcription-PCR. J Clin Microbiol, 41(2):831-834. PMID: 12574294, PMCID: PMC149710.

Westwater C, Schofield DA, Schmidt MG, Norris JS and Dolan JW. 2002. Development of a P1 phagemid system for the delivery of DNA into Gram-negative bacteria. Microbiology, 148(4):943-950. PMID: 11932441.

Hairfield ML, Westwater C and Dolan JW. 2002. Phosphatidylinositol 4-phosphate 5-kinase activity is stimulated during temperature-induced morphogenesis in Candida albicans. Microbiology, 148(6):1737-1746. PMID: 12055293.

Schofield DA, Westwater C, Dolan JW, Norris JS and Schmidt MG. 2002. Tight regulation and modulation via a C1-regulated promoter in Escherichia coli and Pseudomonas aeruginosa. Curr Microbiol, 44(6):425-430.

Schofield DA, Westwater C, Dolan JW, Norris JS and Schmidt MG. 2002. Doc-mediated cell killing in Shigella flexneri using a C1/LacI controlled expression system. FEMS Microbiol Lett, 215(2):237-242. PMID: 12399040.

Kasman LM, Kasman A, Westwater C, Dolan JW, Schmidt MG and Norris JS. 2002. Overcoming the phage replication threshold: a mathematical model with implications for phage therapy. J Virol, 76(11):5557-5564. PMID: 11991984, PMCID: PMC137030.

Shaw DM, Woods AM, Myers KA, Westwater C, Rahi-Saund V, Davies MJ, Renouf DV, Hounsell EF and Stern PL. 2002. Glycosylation and epitope mapping of the 5T4 glycoprotein oncofoetal antigen. Biochem J, 363(1):137-145. PMID: 11903056, PMCID: PMC1222460.

Awan A, Lucic MR, Shaw DM, Sheppard F, Westwater C, Lyons SA and Stern PL. 2002. 5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis. Biochem Biophys Res Commun, 290(3):1030-1036. PMID: 11798178.